Download Blood Thinners

“Blood Thinners”
Coumadin, Heparin, and
Coagulation Laboratory Testing
Coumadin
and Heparin are Anticoagulants
“Blood thinners” don’t really thin the blood. They are anticoagulants, prescription drugs that
either keep existing blood clots from growing larger or prevent new clots from forming. Normal
clotting is essential to stop blood loss after an injury. But abnormal clotting or thrombosis is clotting
that happens when there is no apparent injury. An abnormal clot in a blood vessel is called a
thrombus, and it may completely plug the vessel. For example, a thrombus may plug an artery that
provides blood to the heart muscle, causing a heart attack, or acute myocardial infarction. Or a clot
may plug a large leg vein, causing deep venous thrombosis. Pieces of venous clots may break off,
travel to the lungs or brain, and plug an artery. These pieces are called emboli. An embolus that
travels to the brain causes a stroke. One that goes to the arteries in the lungs is called a pulmonary
embolism, often fatal.
Anticoagulants are prescribed after a thrombotic event. They are also prescribed to
prevent thrombotic events in high-risk situations. Table 1 lists typical thrombotic events and
situations that require anticoagulant therapy.
Table 1: Thrombotic events that require anticoagulant therapy
Peripheral artery
disease
Acute myocardial
infarction
PAD
Cerebrovascular
accident
Transient ischemic
attack
Deep venous
thrombosis
CVA
Pulmonary
embolism
PE
Atrial fibrillation
AFIB
Orthopedic surgery
and other major
surgery
AMI
TIA
DVT
A clot forms in an artery other than arteries of the heart such as a carotid
artery in the neck, reducing the blood supply to that region.
A clot forms in an artery of the heart, called a coronary artery, cutting off the
blood supply to a portion of the heart muscle. This is usually called a heart
attack.
A clot forms in an artery of the brain, reducing the blood supply and causing
the loss of brain tissue. This is usually called a stroke.
A small clot in an artery of the brain causes a temporary loss of memory, loss
of balance, unconsciousness, or other temporary neurological symptoms.
A clot forms in a large vein in the calf or the leg, causing pain, swelling, a
sensation of heat, and redness. Some DVTs cause a long-term disability
called post-phlebitic syndrome.
A clot forms in a large vein in the leg, a portion breaks off and travels to the
lung, causing death of lung tissue and shortness of breath. May be rapidly
fatal.
A mild irregularity in the heartbeat causes the formation of clots in the atria of
the heart that travel to the brain to cause a CVA.
Doctors prescribe anticoagulants to people who are at risk of a thrombotic
event, such as people who have had hip or knee replacement surgery
A Typical Case Requiring Anticoagulant Therapy
John arrives in the emergency department with severe chest pain. The nurse immediately
gives him an aspirin. A technician performs an EKG and a laboratory scientist draws blood for
laboratory tests. The results soon show that John has an AMI. The doctor treats him with an
intravenous thrombolytic “clot buster” drug to reopen the clogged artery.
Soon, John is started on intravenous heparin and on Coumadin pills. About three days
after he is admitted he goes to the catheterization laboratory where a stent is placed in the artery to
keep it open. He suffers no complications, the heparin is discontinued in five days, and he is
discharged on the sixth.
John must continue to take oral Coumadin for six months. Although a typical dose is one
5-milligram tablet a day, the dosage varies by individual and it varies over time. Once a month he
comes to the hospital laboratory or an outside laboratory to have a blood test called a prothrombin
time (“protime,” PT), and he has to adhere to a “Coumadin diet” until the end of the therapy.
John also takes antiplatelet drugs; aspirin and Plavix . He will discontinue the Plavix
after one year but will continue taking one baby aspirin a day for the rest of his life.
What Is Heparin For?
Heparin is an immediate-acting anticoagulant that has been used successfully since 1945.
It is administered intravenously, so it is convenient only for inpatients. Also, heparin actually causes
thrombosis in about 1% of patients, so it has to be carefully monitored by daily laboratory testing.
How Does the Laboratory Test for Heparin?
During the first day that John was getting his IV heparin, his blood was drawn every six
hours. During days two through four, his blood was collected every 24 hours. The specimen went
to the laboratory, where scientists performed the activated partial thromboplastin time (APTT or
PTT) test.
Heparin affects everyone differently, so there is no standard dose. The doctor or nurse
must repeatedly adjust the heparin dosage to achieve and maintain a therapeutic PTT result. In
John’s hospital, the therapeutic PTT value was 65 to 95 seconds, but this varies by the hospital.
If the PTT shortens to below the therapeutic range, John would be in danger of having a
second heart attack. Often second attacks are fatal. PTT results that are longer than the high limit
indicate a risk of bleeding.
What is Coumadin
For?
Coumadin is the only anticoagulant that can be taken orally, so it is used for long-term
anticoagulant therapy. It is one of the top twenty most prescribed drugs in the United States and
comes in at least four forms as are listed in table 2.
Table 2: Names of the various forms of oral anticoagulants
Coumadin (most common brand)
Warfarin (oldest brand name)
Coumarin
Dicumarol
The various forms of Coumadin all work the same and are reliable, although the required
dosage may vary by brand. It takes Coumadin about five days to become effective and therapy
usually lasts for six months or longer, depending upon the patient’s condition. For example, people
with atrial fibrillation may take Coumadin their whole lives to prevent a stroke, people with an AMI
are usually treated for six months.
Coumadin is Dangerous and Hard to Control
Coumadin prevents a new clot from forming or an existing clot from growing. If a patient is
taking too little Coumadin, it will not provide this protection and a new clot may form. Conversely,
too much Coumadin causes bleeding, often severe enough to require hospitalization.
The Coumadin dosage is hard to control. There are at least 100 drugs (table 3) that affect
Coumadin, either by increasing or decreasing its effect. Further, green vegetables decrease
Coumadin, and some dietary supplements may either decrease or increase Coumadin, so careful
dosage adjustments are needed (tables 4 and 5). Some drugs and supplements affect platelets,
blood cells that help in blood clotting, thereby increasing the risk of bleeding.
Table 3: Classes of drugs that may either increase or decrease the effect of Coumadin
Antibiotics of many types
Anti-inflammatory drugs including aspirin and ibuprofen
Anti-malarial drugs such as quinidine
Anti-seizure drugs such as Dilantin
Chemotherapy for cancer
Drugs for treatment of gout
Drugs for treatment of stomach disorders
Lipid lowering drugs such as Pravachol or Lipitor
Psychiatric drugs like Thorazine
Table 4: Foods and dietary supplements that reduce the effect of Coumadin
Coenzyme-Q, a free radical scavenger
Ginseng and green tea
Green leafy vegetables and salads
Green tea
Liver
Table 5: Dietary supplements that appear to increase the effect of Coumadin or that
contribute to bleeding by disabling platelets
Angelica root
Anise
Chamomile
Dong quai
Feverfew
Garlic
Ginger
Ginkgo biloba
Meadowsweet (aspirin-like substance from Spirea shrub)
Papain (papaya-based tenderizer)
Vitamin E, an antioxidant
How Does the Laboratory Test for Coumadin? The INR
Let’s return to our case. When John started getting his IV heparin, he also started taking
Coumadin. The same blood specimens that went to the laboratory for a PTT to monitor heparin
were used to perform a second test, the prothrombin time (PT). The PT is similar to the PTT, but it
is more sensitive to Coumadin and the result is reported not in seconds but as an international
normalized ratio (INR).
The INR is the ratio between the time it takes normal blood to clot and Coumadin blood to
clot. The more Coumadin, the higher the INR. Most people taking Coumadin should have an INR
between 2 and 3. An INR below 2 signals the danger of a new clot, whereas an INR over 4 means
a risk of dangerous bleeding. The INR, as the name implies, is international, so it should be
comparable no matter where the test is performed.
While he was in the hospital, John’s PT was tested once a day until it reached an INR
between 2 and 3. Then it was tested once every two weeks for the first three times, and then once
a month for as long as he took Coumadin. Why once a month? Coumadin dosages need constant
adjustment as we change our diet, our habits, or our other medicines. If John waits two months to
have his PT performed, his INR could drift out of control.
Doctors and patients would prefer to use substitutes for heparin and Coumadin that are
safer and require less laboratory testing, and researchers everywhere are looking for these new
drugs. Until they are successful, however, regular laboratory testing is the only answer.
For more information, contact the UAB Coagulation Service
George A. Fritsma MS MT (ASCP)
Coordinator, UAB Coagulation Service
P: 205-934-1348; F: 205-975-4468